The goal of the present application is to provide continued support for training postdoctoral fellows in neurobiology and biological psychiatry with particular emphasis on the biology of mood disorders. This program exists in the context of the Mental Health Research Institute (MHRI) of the University of Michigan Medical Center, and has been funded by the NIMH for over a quarter of a century. The present application represents a refocusing of the program to emphasize training in modern methods of neurobiology-including genetics, molecular biology, neuroanatomy, signal transduction, neuroendocrinology, neuroimaging-and their relevance to depression and anxiety disorders. This plan represents a continuation of our past efforts at fostering close interactions between physicians and basic scientists in arenas of relevance to understanding brain function and dysfunction. However, it has been sharpened in a number of ways to strengthen this interface and provide our trainees with a coherent and focused program: 1) Research and training efforts will be focused on a shared strength between the MHRI and the Psychiatry Department-i.e., the biology of stress and mood disorders. 2) We have expanded our faculty to 29 members, including a number of young, well-trained neuroscientists and biological psychiatrists. 3) Particular emphasis is placed on giving the physician trainees the opportunity to acquire both a conceptual and working knowledge of modern molecular approaches. This will be achieved through laboratory exposure, and through a working seminar series focused on in-depth discussion of studies ranging from the molecule to the clinic. 4) Our basic science trainees will be required to attend a course in biological psychiatry with the psychiatry residents, to get a sense of the current critical questions in this area. Support for 5 trainees per year is requested. All trainees will hold either the MD degree of the PhD degree. All would be tasked to selected mentors among the faculty and define a specific and coherent research proposal. Trainees will have a primary research mentor to direct research efforts and a secondary mentor to expand their knowledge in needed fields. In cases where the selected mentor is young and has limited training experience, an appropriate senior co-mentor will be chosen to ensure excellent support for the trainee. This program has graduated a significant number of excellent trainees, several of them physicians, who have gone on to research careers in academic institutions. It has also trained several members of disadvantaged minorities who have been very successful. This NIMH Training Grant will be administered by the Program Director who is the Co-Director of the MHRI and Associate Chair for Research in Psychiatry. He will be assisted by an Executive Committee, which will help in the selection of fellows, will share in the distribution of slots, and will oversee the courses relevant to this training grant, including the ethics series. The trainees will have access to world- class facilities and laboratories, in the context of a rich and supportive environment.